RNA interference (RNAi) is a form of post-transcriptional gene silencing in which double-stranded RNA (dsRNA) induces the enzymatic degradation of homologous messenger RNA (mRNA). When a long dsRNA enters a cell, an enzyme called Dicer binds and cleaves the long dsRNA. Cleavage by Dicer results in the production of a small interfering RNA (siRNA) that is generally 20-25 base pairs (bp) in length and has a 2-nucleotide long 3′ overhang on each strand. One of the two strands of each siRNA, generally the antisense strand, is then incorporated into an RNA-induced silencing complex (RISC), and pairs with complementary RNA sequences. RISC first mediates the unwinding of the siRNA duplex, a single-stranded siRNA that is coupled to RISC, then binds to a target mRNA in a sequence-specific manner. The binding mediates target mRNA cleavage by Slicer, an argonaute protein that is the catalytic component of RISC. Cleavage of the mRNA prevents translation from occurring, which prevents the ultimate expression of the gene from which the mRNA is transcribed. Now, it has been confirmed that RNAi has great potential treatment of a variety viral infections, and it is the ideal treatment for blocking gene expression.
RNAi has tremendous potential in medicinal therapeutics, such as in anti-viral, oncogenic and anti-inflammatory applications. The double-stranded siRNA may be a long double-strand designed to be cleaved by Dicer, called Dicer substrate, or it may be short and is designed to bypass Dicer serve directly as a RISC substrate. The dsRNAs are synthesized with a sequence complementary to a gene of interest and introduced into a cell or organism, where they are recognized as exogenous genetic materials and activate the RNAi pathway. RNAi can cause a drastic decrease in the expression of a targeted gene by using this mechanism.
RNAi can be used to develop a whole new class of therapeutics. Currently there are more than ten kinds of siRNA drug at the clinic stage. Among the applications to reach clinical trials are treatment of age-related macular degeneration, diabetic retinopathy, and respiratory syncytial virus, solid tumors, liver cancer, and acute kidney injury and other diseases.